David A. Pegues, MD
What are the relative efficacy and harms of antibiotic treatments for Clostridium difficile infection in adults?
Included studies evaluated drugs available in the USA for treatment of C. difficile infection in adults. Outcomes included initial cure, recurrence, mortality, and duration of diarrhea.
MEDLINE, Allied and Complementary Medicine, Cochrane databases, and ClinicalTrials.gov (all to Aug 2011); US Food and Drug Administration Web site; and reference lists were searched for full-text, English-language, randomized, controlled trials (RCTs). Experts were contacted. 11 RCTs (n = 1463, mean age range 42 to 69 y, 40% to 99% men, range of posttreatment follow-up 21 to 60 d) met inclusion criteria: 3 compared vancomycin with metronidazole (n = 399), 5 compared vancomycin with other agents (bacitracin, n = 104; nitazoxanide, n = 50; fidaxomicin, n = 629) or placebo (n = 44), 1 compared metronidazole with nitazoxanide (n = 142), 1 compared metronidazole alone with metronidazole plus rifampin (n = 39), and 1 compared different doses of vancomycin (n = 56). 6 RCTs reported adequate allocation concealment, 6 had blinding of patients and study personnel, and 3 used intention-to-treat analysis. Data were not pooled because of study heterogeneity.
In individual trials, fidaxomicin reduced risk for recurrence of C. difficile infection more than vancomycin (n = 602), vancomycin increased initial cure rate more than placebo (n = 21), and adding rifampin to metronidazole increased mortality (n = 39) (Table). Other comparisons did not differ for initial cure, infection recurrence, mortality, or duration of diarrhea (Table).
Fidaxomicin is better than vancomycin for preventing recurrence of Clostridium difficile infection in adults; vancomycin and metronidazole do not differ for initial cure or recurrence. Insufficient evidence exists to evaluate other antibiotics.
Effectiveness of antibiotics in Clostridium difficile infection in adults*
*RCT = randomized controlled trial.
†n = number included in systematic review. Strength of evidence (Agency for Healthcare Research and Quality and the Effective Health Care Program criteria) was low or insufficient unless otherwise indicated.
‡Strength of evidence = moderate.
§Calculated from data in article using the Fisher exact test.
Pegues DA. Review: Fidaxomicin is better than vancomycin for Clostridium difficile recurrence. Ann Intern Med. ;156:JC4–9. doi: 10.7326/0003-4819-156-8-201204170-02009
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Published: Ann Intern Med. 2012;156(8):JC4-9.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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